Variations in daily food intake are quite large in free- living individuals and not well synchronized with variations in energy expenditure (EE). Although this leads to substantial short term energy imbalances, long-term errors in the energy balance are generally remarkably small (e.g. less than the 2 percent of energy turnover over a year). Because changes in EE elicited by food intake attenuate only slightly the impact of over- or under-eating, weight maintenance depends primarily on appropriate adjustment of food intake of EE. The body's glycogen reserved are not much greater than the amount of carbohydrate (CHO) habitually consumed in one day. Evolution was therefore compelled to develop regulatory features giving especially high priority to the maintenance of CHO balance. An important issue in understanding body weight regulation, when access to food in unrestricted, is whether maintenance of stable glycogen reserves is achieved merely through adjustment of glucose oxidation to CHO intake, or whether this may be helped by influences induced by changing glycogen levels on food intake. However, given the loose control of daily energy intake and balance, it is difficult to establish whether this, and/or other mechanisms are involved in bringing about appropriate 'corrective changes' in food intake. To gain some insight about these difficulties, the development of a computer model of human energy metabolism was undertaken. It uses the Systems Dynamics approach in which changes in the content of various compartments are computed over consecutive time intervals. The course of events can be displayed in tables and graphs as a function of time, over hours, or hundreds of days. When conditions are kept constant, the simulations lead in time to steady-states; if aberrant configurations are reached, they suggest the changes which need to be implemented in the model to make it progressively more consistent with current knowledge of substrate metabolism in man. This grant application seeks funds to pursue the development of the a computer model constructed by integration of subsystems which themselves are models of substrate metabolism in the body's major organs. In time, a user-friendly interface will be developed enabling investigators, students, dieticians, nutritionists and others to have an interactive opportunity to obtain images of substrate metabolism in man and to observe its responses to conditions which can be specified and altered by the user.